Various prostaglandins are useful for the treatment of medical conditions including, for example: ocular disorders, such as glaucoma; skin disorders; circulatory disorders, such as hypertension; gastrointestinal disorders; hair loss; respiratory disorders; fertility control; and bone disorders, such as osteoporosis. Information regarding the biological effects of Prostaglandin F analogs is disclosed in the following references: PCT Publication No. WO 99/12895, 1999; PCT Publication No. WO 99/12896, 1999; PCT Publication No. WO 99/12898; Abstr. 1999, 194116 “Molecular mechanisms of diverse actions of prostanoid receptors”, Biochimica et Biophysica Acta, 1259 (1995) 109-120; U.S. Pat. No. 3,776,938 issued to Bergstrom, S., and Sjovall, J., Dec. 4, 1973; U.S. Pat. No. 3,882,241 issued to Pharriss, G., May 6, 1975; G.B. Patent No. 1,456,512 (1976) issued to Pfizer Inc., Bundy, G. L.; Lincoln, F. H., “Synthesis of 17-Phenyl-18,19,20-trinor prostaglandins I. The PG1 Series”, Prostaglandins Vol. 9 (1975) pp. 1-4.; CRC Handbook of Eicosanoids: Prostaglandins and Related Lipids Vol. 1, Chemical and Biochemical Aspects, Parts A & B, A. L. Willis, eds., CRC Press (1987); Liljebris, C.; et. al. “Derivatives of 17-Phenyl-18,19,20-trinorprostaglandin F2α Isopropyl Ester: Potential Antiglaucoma Agents”, Journal of Medicinal Chemistry Vol. 38, (1995), pp. 289-304; Collins, P. W.; Djuric, S. W. “Synthesis of Therapeutically Useful Prostaglandin and Prostacyclin Analogs”, Chemical Reviews 93 (1993), pp. 1533-1564.
All naturally occurring prostaglandins, including PGF2α, and almost all non-naturally-occurring prostaglandins possess a carboxylic acid moiety at the C1 position. The carboxylic acid moiety is a site for metabolic degradation by beta oxidation, which contributes to the rapid metabolism of the naturally occurring prostaglandins. Attempts to prevent beta oxidation by modifying the carboxylic acid moiety at the 1 position as an ester moiety, a sulfonamide moiety, and as a tetrazole are known in the art (See e.g. PCT Publication No. WO 99/12895, 1999; PCT Publication No. WO 99/12896, 1999; PCT Publication No. WO 99/12898). However, such modifications have either resulted in only modest increases in half-life (such as the esters) or resulted in compounds with diminished potency.
Prostaglandin F analogs wherein C1 itself is replaced with a heteroatom have also been described in the art. For example, PGF analogs containing a sulfonic acid moiety at C1 (The chemistry of prostaglandins containing the sulfo group. Iguchi, Y.; Kori, S.; Hayashi, M. J. Org. Chem., 40, pp. 521-523 1975) and PGF analogs containing a phosphonic acid moiety at C1 (The Synthesis of dimethylphosphonoprostaglandin analogs, Kluender, H. C. & Woessner, W. Prostaglandins and Medicine, 2: pp. 441-444, 1979) have been disclosed. However, such compounds suffer from significantly diminished potency. However, the potent C1 carboxylic acids are difficult to purify as they are most often synthesized as oils. There is a need for solid forms of prostaglandins, both naturally and non-naturally occurring, for the purposes of purification and as intermediates in synthesis, as well as the direct use of these solids in drug products.